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  7. STKR Type 2 subfamily
  8. TGF-beta receptor type-2

Tchem TGF-beta receptor type-2

Transmembrane serine/threonine kinase forming with the TGF-beta type I serine/threonine kinase receptor, TGFBR1, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3. Transduces the TGFB1, TGFB2 and TGFB3 signal from the cell surface to the cytoplasm and is thus regulating a plethora of physiological and pathological processes including cell cycle arrest in epithelial and hematopoietic cells, control of mesenchymal cell proliferation and differentiation, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. The formation of the receptor complex composed of 2 TGFBR1 and 2 TGFBR2 molecules symmetrically bound to the cytokine dimer results in the phosphorylation and the activation of TGFRB1 by the constitutively active TGFBR2. Activated TGFBR1 phosphorylates SMAD2 which dissociates from the receptor and interacts with SMAD4. The SMAD2-SMAD4 complex is subsequently translocated to the nucleus where it modulates the transcription of the TGF-beta-regulated genes. This constitutes the canonical SMAD-dependent TGF-beta signaling cascade. Also involved in non-canonical, SMAD-independent TGF-beta signaling pathways.

The protein encoded by this gene is a transmembrane protein that has a protein kinase domain, forms a heterodimeric complex with TGF-beta receptor type-1, and binds TGF-beta. This receptor/ligand complex phosphorylates proteins, which then enter the nucleus and regulate the transcription of genes related to cell proliferation, cell cycle arrest, wound healing, immunosuppression, and tumorigenesis. Mutations in this gene have been associated with Marfan Syndrome, Loeys-Deitz Aortic Aneurysm Syndrome, and the development of various types of tumors. Alternatively spliced transcript variants encoding different isoforms have been characterized. [provided by RefSeq, Aug 2017]

 Comments

Property Summary

Ligand Count 9
NCBI Gene PubMed Count 438
PubMed Score 665.12
PubTator Score 615.96

Knowledge Summary

Patent (16,731)

TINX Plot

  Disease (7)

Disease Target Count
Abdominal Pain 98
Abnormality of the iris 14
Abnormality of the voice 46
Acquired flat foot 72
Acquired scoliosis 281
Aneurysm of ascending aorta 5
Anxiety 136
Anxiety disease 113
Aortic Valve Insufficiency 40
Aortic aneurysm, familial thoracic 3 13
Arachnodactyly 49
Arterial tortuosity 5
Arterial tortuosity, generalized 2
Ascending aortic dissection 13
Attention deficit hyperactivity disorder 278
Atypical scarring of skin 62
Blue sclera 32
Brachydactyly 156
Byzanthine arch palate 194
Cardiomegaly 116
Chest Pain 38
Cleft palate with cleft lip 23
Cleft uvula 27
Clinodactyly of the 5th toe 6
Congenital Camptodactyly 40
Congenital clubfoot 109
Constipation 181
Contracture of joint of hand 30
Coronary artery disease 268
Coughing 25
Craniosynostosis 74
Curvature of spine 282
Curvature of the little toe 6
Cutis marmorata 32
Cystic medial necrosis of aorta 13
Death in early adulthood 24
Death in early childhood 82
Death in infancy 82
Depressive disorder 409
Descending aortic dissection 13
Diabetic Nephropathy 34
Dissection of aorta 9
Dyschezia 135
Dyspnea on exertion 24
Dyspnea, Paroxysmal 13
Epilepsy 792
Esophageal carcinoma 16
Exophthalmos 112
Exotropia 35
Feeding difficulties in infancy 175
Flatfoot 73
Flexion contracture of proximal interphalangeal joint 75
Gastrointestinal Hemorrhage 52
Hereditary Nonpolyposis Colorectal Cancer 11
Hereditary Nonpolyposis Colorectal Neoplasms 8
Hereditary nonpolyposis colorectal carcinoma 18
Hypertensive disease 292
Hypoplastic mandible condyle 275
Hypotrophic malar bone 129
Impaired left ventricular function 16
Increase in blood pressure 119
Intermittent migraine headaches 68
Intracranial hypertension 32
Irritation - emotion 68
Joint laxity 54
Left-Sided Heart Failure 16
Linear atrophy 15
Loeys-Dietz Aortic Aneurysm Syndrome 13
Malabsorption 82
Malar flattening 129
Malignant Squamous Cell Neoplasm 17
Malignant tumor of colon 19
Mandibular hypoplasia 275
Marfan Syndrome type 2 1
Micrognathism 275
Muscle Hypertonia 88
Muscle hypotonia 571
Nausea and vomiting 97
Oral cleft 18
Orbital separation excessive 244
Patent ductus arteriosus 90
Prominent eyes 96
Prominent globes 96
Protruding eyes 96
Pulmonary artery aneurysm 2
Rectal Neoplasms 18
Retrognathia 54
Schizophrenia 1160
Seizures 596
Skull malformation 38
Squamous cell carcinoma 129
Sternal anomalies 19
Tall stature 34
Translucent skin 4
Uterine Rupture 2
Weight decreased 103
glioblastoma 5792
Disease Target Count Z-score Confidence
pancreatic cancer 2398 0.0 0.6

Expression

  Differential Expression (32)

Disease log2 FC p
Breast cancer -2.400 1.8e-15
glioblastoma 2.400 1.1e-04
active ulcerative colitis 1.338 1.1e-02
acute quadriplegic myopathy 1.507 8.5e-05
adrenocortical carcinoma -1.450 8.8e-04
Astrocytoma, Pilocytic 1.800 1.6e-07
autosomal dominant Emery-Dreifuss muscul... 1.333 7.1e-03
Becker muscular dystrophy 1.002 1.8e-02
breast carcinoma -1.400 1.5e-04
COPD -1.100 6.2e-03
cystic fibrosis 2.504 2.3e-06
dermatomyositis 2.200 1.7e-03
Duchenne muscular dystrophy 1.708 6.3e-08
ductal carcinoma in situ -1.100 8.9e-03
ependymoma 1.100 3.8e-05
Gaucher disease type 1 -2.300 1.7e-02
invasive ductal carcinoma -2.200 1.7e-04
juvenile dermatomyositis 1.484 9.4e-10
limb girdle muscular dystrophy 2A 1.190 2.3e-04
lung adenocarcinoma -1.300 6.0e-17
lung cancer -1.600 6.5e-03
lung carcinoma -2.100 1.6e-21
malignant mesothelioma -2.000 3.5e-07
mucosa-associated lymphoid tissue lympho... 1.018 3.3e-02
nephrosclerosis 1.026 1.1e-03
non-small cell lung cancer -1.183 1.4e-08
osteosarcoma 1.792 1.9e-04
ovarian cancer -3.200 1.2e-09
pancreatic ductal adenocarcinoma liver m... -1.488 2.5e-02
pediatric high grade glioma 1.200 7.4e-03
sonic hedgehog group medulloblastoma 1.400 5.1e-04
Waldenstrons macroglobulinemia 1.012 2.5e-02

Synonym

Accession P37173 B4DTV5 Q15580 Q6DKT6 Q99474 TGFR-2
Symbols AAT3
FAA3
LDS2
MFS2
RIIC
LDS1B
LDS2B
TAAD2
TBRII
TBR-ii
TGFR-2
TGFbeta-RII

Gene

TGFBR2

PANTHER Protein Class (4)

  Ortholog (13)

Species Source Disease
OMA EggNOG
Inparanoid OMA EggNOG
Inparanoid OMA EggNOG
Inparanoid OMA EggNOG
Inparanoid OMA EggNOG
Inparanoid OMA EggNOG
OMA EggNOG
Inparanoid OMA EggNOG
Inparanoid OMA EggNOG
Inparanoid OMA EggNOG
OMA EggNOG
Inparanoid OMA EggNOG
Inparanoid OMA EggNOG

 UniProt Keyword (29)

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 GO Function (12)

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 GO Component (8)

 GO Process (70)

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 Compartment GO Term (49)

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 OMIM Phenotype (3)

 MGI Phenotype (21)

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 GWAS Trait (7)

 HCA RNA Cell Line (56)

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 CSPA Cell Line (11)

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Pathway (68)

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Protein-protein Interaction (26)

PIK3CB   CDC6   PKN3   PLEKHH3   ACVR2B   PKN2   JAK1   PIK3R2   PIK3R1   PIK3R3   RAB6B   MARCH7   RELT   BMPR1A   ERBB2   DENND6A   FGFR1   PTPRS   NDFIP1   MFAP3   MYADM   SBF1   FMN2   LRP10   NEDD8   CBL  

PDB (13)

Ligand (9)

Structure of CHEMBL2385582

CHEMBL2385582
pIC50 7.59

Structure of CHEMBL2385600

CHEMBL2385600
pIC50 7.80

Structure of CHEMBL2385596

CHEMBL2385596
pIC50 7.82

Structure of CHEMBL2385579

CHEMBL2385579
pIC50 8.86

Structure of compound 13a [PMID: 23639540]

compound 13a [PMID: 23639540]
pIC50 8.86

Structure of compound 13d [PMID: 23639540]

compound 13d [PMID: 23639540]
pIC50 7.59

Structure of compound 15b [PMID: 16539403]

compound 15b [PMID: 16539403]
pIC50 6.45

Structure of galunisertib

galunisertib
pIC50 6.68

Structure of LY2109761

LY2109761
pKi 6.52

Gene RIF (365)

AA Sequence 

MGRGLLRGLWPLHIVLWTRIASTIPPHVQKSVNNDMIVTDNNGAVKFPQLCKFCDVRFSTCDNQKSCMSN      1 - 70
CSITSICEKPQEVCVAVWRKNDENITLETVCHDPKLPYHDFILEDAASPKCIMKEKKKPGETFFMCSCSS     71 - 140
DECNDNIIFSEEYNTSNPDLLLVIFQVTGISLLPPLGVAISVIIIFYCYRVNRQQKLSSTWETGKTRKLM    141 - 210
EFSEHCAIILEDDRSDISSTCANNINHNTELLPIELDTLVGKGRFAEVYKAKLKQNTSEQFETVAVKIFP    211 - 280
YEEYASWKTEKDIFSDINLKHENILQFLTAEERKTELGKQYWLITAFHAKGNLQEYLTRHVISWEDLRKL    281 - 350
GSSLARGIAHLHSDHTPCGRPKMPIVHRDLKSSNILVKNDLTCCLCDFGLSLRLDPTLSVDDLANSGQVG    351 - 420
TARYMAPEVLESRMNLENVESFKQTDVYSMALVLWEMTSRCNAVGEVKDYEPPFGSKVREHPCVESMKDN    421 - 490
VLRDRGRPEIPSFWLNHQGIQMVCETLTECWDHDPEARLTAQCVAERFSELEHLDRLSGRSCSEEKIPED    491 - 560
GSLNTTK                                                                   561 - 567
//

Text Mined References (451)

PMID Year Title